Hair follicle is a peculiar skin organ of mammals. At the base of the hair follicle is a large structure that is called papilla (Stenn and Paus, Physiol. Rev., 81: 449 (2002)). The papilla is essential in normal circulation of the hair follicle (Oliver, Embryol. Exp. Morph. 15: 331 (1966); Oliver, Embryol. Exp. Morph. 16: 231 (1967)) and in growth of the hair shaft. The hair shaft is a thread-shaped structure prepared from epithelial cells, composed of keratin filaments and filament-aggregating proteins tightly attached thereto.
Human hair follows a growth cycle with three distinct phases: anagen, catagen, and telogen phases. The hair growth cycle is regulated by hormones or many growth factors. Severe stress or malnutrition may advance the catagen and telogen phases, leading to severe hair loss (alopecia) (Vladimir A. Botchkarev, American Journal of Pathology, 162 (3): 709-712 (2003)).
In male pattern baldness, the hair follicles at the front and top of the scalp are sensitive to androgen, which causes the follicles to shrink or miniaturize, thereby resulting in hair loss. In 20% of women, the hair often becomes thinner at the top of the scalp, resulting in “female pattern baldness”. The hair loss broadens with aging. Also, cicatricial alopecia caused by injury, disease or burns may cause severe hair loss. Whatever is the cause, hair loss may have remarkable psychological, social and sexual impacts as well as loss of pride and self-respect. Although various drugs have been used to treat hair loss, they are too expensive or give very different results among individuals.
In cosmetic products, inexpensive but less effective plant extracts have been used, which do not give good result. To overcome these problems, keratinocyte growth factor derived from human has been produced in large scale through fermentation and purification using E. coli, and the nanosome technology has been developed to improve skin permeability. Also, the effect has been further improved by adding keratinocyte growth factor-derived peptides. Keratinocyte growth factor facilitates the anagen phase during which hair is produced and grows. It retains the hair cycle at the anagen, thereby reducing hair loss caused by various environmental factors, and, in normal hair, it contributes to the growth and health of hair by supplying nutrients. The treatment of and solution to hair loss have changed greatly with time. Although baldness can be covered using wigs or toupees or by expanding hair, they do not lead to hair regrowth. And, although the two currently available drugs (minoxidil and finasteride) known thus far can delay further hair loss, they do not induce regeneration of hair follicles. Many hair care cosmetics for preventing hair loss using plant extracts have been released in the market. Especially, the products using extracts of sophora, hot pepper, black pepper, mulberry root, mulberry leaf, ginseng, licorice, peony, foxglove, fennel, Japanese cornel, garlic, etc., the products prepared to improve cellular metabolism suppressed by excess dihydrotestosterone (DHT) and to facilitate hair regeneration and growth by adding compositions containing xanthines and growth hormones, the products prepared to supply nutrients to the scalp and hair and to prevent hair loss and promote hair growth by adding minerals, vitamins and extracts of green tea, rosemary, mugwort and licorice, and the male pattern baldness products prepared to suppress production of DHT during androgen metabolism by inhibiting 5-alpha reductases and to help hair metabolism by mixing the substances such as vitamin B, vitamin C, vitamin D, vitamin E, nicotinic acid, pantothenic acid, biotin, folic acid, etc. with plant extracts have been developed. But, they hardly affect the production of new hair. Also, the products inhibiting 5-alpha reductases and exhibiting excellent hair growth effect have been developed by using, for example, corosolic acid, which was shown to be effective in diabetes, etc. by a research group of the Jikei University School of Medicine in Tokyo, Japan.
Many factors are involved in the growth and degeneration of hair. The inventors of the present disclosure have studied the growth factors that promote hair production and growth by activating keratinocyte growth factors and vascular endothelial growth factors and suppressing activity of BMP proteins. In particular, they have produced noggin proteins, which suppress BMP2/4 that inhibits the human-derived keratinocyte growth factors FGF-7 (KGF) and FGF-10 involved in hair cycle and retards the initiation of anagen during the hair follicle growth, in large scale through fermentation and purification using E. coli and developed them into growth factor-containing cosmetics to promote hair growth and prevent hair loss (Korean Patent No. 1007968170000; Growth factor for hair and skin treatment). Although the growth factors provide excellent effect, additional process and time for refolding are required to obtain wild-type growth factors. Further, a complicated purification process is necessary to remove the source of contamination derived from E. coli, and the stability and high molecular weight problems as well as high cost make it less applicable.
In order to solve the problems associated with the expression of growth factors, there have been attempts to produce only part of some growth factors by solid-phase synthesis to achieve a similar function. For example, in U.S. Pat. No. 5,473,054, Jameson et al. have named the 29-38 and 61-70 fragments of IGF-1 respectively as JB2 and JB1, and reported the effect of the peptide fragments on cellular growth as well as the inhibitory effect of JB3, an enantiomer of JB1, against IGF-1. Also, Teruo et al. have reported in WO 03/048192 the complementary action of the 33-37 fragment of IGF-1 and a substance P-derived tetrapeptide in wound healing. In addition, Kodama et al. have reported in Autoimmunity 37: 481-487 (2004) that the 50-70 fragment of IGF-1 helps treatment of diabetes in mouse.
Throughout the specification, a number of publications and patent documents are referred to and cited. The disclosure of the cited publications and patent documents is incorporated herein by reference in its entirety to more clearly describe the state of the related art and the present disclosure.